This project, which provides state-of-the-art psychophysical methodology for other Center projects, focuses on the development of olfactory tests of practical use in the clinic and their application to a variety of disease states. In Experiment 1, we will continue to develop and refine clinical olfactory tests (e.g., tests or odor detection, memory, and suprathreshold intensity and pleasantness perception), with the goal of finding an optional set of test for inclusion in a clinically-useful olfactory test battery. Such factors as test-retest reliability, ease of test administration, bilateral vs. unilateral test administration, and the degree of interrelation among tests will be explored. In experiments 2, we will administer a variety of olfactory tests to individuals with well-characterized neurological and endocrine disorders associated, on theoretical or empirical grounds, with olfactory dysfunction in order to (i) establish the relative efficacy of these tests in detecting olfactory dysfunction, (ii) determine the degree to which various tests correlate with one another in specific patient populations, and (iii) better understand the nature of the olfactory dysfunction in such disorders. Among the diseases to be studied are familial Parkinson's disease (fPD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), multi- infarct dementia (MD), schizophrenia (SZ), retinitis pigmentosa (RP), Usher's syndrome (US), pseudohypoparathyroidism (PHP) and epilepsy. fPD was chosen to determine if an inherited form of PD is accompanied by the same degree of olfactory dysfunction as idiopathic (i.e., sporadic) PD. ALS is of interest because of evidence of some olfactory dysfunction in patients with predominantly ALS symptoms in the ALS/PD/dementia complex of Guam. RP and US were selected largely on the basic of (i) anecdotal reports of olfactory loss in these disorders and (ii) their association with cilia-related pathology in the eye and inner ear--pathology which may also be present in olfactory receptor cells. PHP was chosen because of reports of olfactory problems associated with G alpha-deficient forms of this disease, whereas SZ and MID were chosen because of earlier reports of olfactory loss in these disorders and the need to better understand the nature and magnitude of this loss. Patients who undergo neurosurgery for intractable epileptiform seizure activity are of particular interest to us, since such operations impinge upon brain regions associated with central olfactory processing. In such cases, we plan to compare the efficacy of our olfactory tests in characterizing the sensory dysfunction before and after the surgical resection. Importantly, we will determine (i) the nature and degree of olfactory dysfunction that is present on each side of the nose prior to surgery, (ii) the extent to which such surgery influences ipsilateral and contralateral function, (iii) whether age at first risk for seizures is related to the degree of preoperative and postoperative olfactory dysfunction, and (iv) whether and to what degree olfactory function changes over a five-year postoperative period. Overall, the experiments of this program will further advance the development of clinical olfactory tests and will provide insights into the nature and prevalence of chemosensory dysfunction in a wide range of medical disorders.